Protease-mediated FGF-2 release and body stature. (A) Whole-body micro-CT images of 8-wk-old WT, QT, QT3^+/−, J-QT3^+/−, and C-QT3^+/− mice. Images allow comparison of disproportion in the femur and tibia lengths, sternum, and spine curvature among different genotypes (yellow line, length of sternum; orange line, extent of kyphosis; blue line, femur length). Scale bar = 10 mm. (B) Cartoon depicting the effect of aggrecan cleavage by MMPs on bone length. The lack of MMP regulation by TIMPs (excess MMP activity) results in growth plate aberrations in the long bones, while the lack of MMP processing has the profound effect of shortening the sternum. (C) Distal femoral head explant culture to determine FGF-2 level by ELISA on the femoral distal head culture supernatant of WT (n = 10), QT3^+/− (n = 4), J-QT3^+/− (n = 3), and C-QT3^+/− (n = 5) mice. Reduction of FGF-2 release from contralateral femoral head by BB94 treatment, determined by ratio paired t test. Each box of box-and-whisker plot shows second to third quartile of datasets and line within the box shows median; *, P < 0.05. (D) Pictorial summary delineating the role of TIMPs in molecular processing to alter the bone length. Activation of the FGFR by excessive metalloprotease release of perlecan-bound FGF2 represses IHH-mediated chondrocyte maturation.